title: Hypercapnic acidosis attenuates severe acute bacterial pneumonia-induced lung injury by a neutrophil-independent mechanism.
abstract: OBJECTIVE
  Deliberate induction of hypercapnic acidosis protects against lung injury after nonseptic lung injury. In contrast, concerns exist regarding the effects of hypercapnic acidosis in the setting of severe pulmonary sepsis. The potential for the effects of hypercapnic acidosis to be neutrophil-mediated remains to be determined. We investigated whether hypercapnic acidosis--induced by adding CO2 to inspired gas--would protect against severe acute lung injury induced by pulmonary Escherichia coli instillation and the role of neutrophils in mediating this effect.
  
  
  METHODS
  Prospective randomized animal study.
  
  
  METHODS
  University Research Laboratory.
  
  
  METHODS
  Adult male Sprague-Dawley rats.
  
  
  METHODS
  In series 1, after induction of anesthesia and tracheostomy placement, animals were randomized to normocapnia (FICO2 0.00, n = 12) or hypercapnic acidosis (FICO2 0.05, n = 12). E. coli (0.5-3.0 x 10(15) colony-forming units) was instilled intratracheally and the animals were ventilated for 6 hrs to allow a severe acute lung injury to evolve. In series 2, animals were randomized to neutrophil depletion or nondepletion before bacterial instillation, in a three-group design: normocapnia alone (Normo + polymorphonuclear neutrophils [PMN], n = 9), normocapnia with neutrophil depletion (Normo - PMN, n = 9), or hypercapnic acidosis with neutrophil depletion (hypercapnic acidosis - PMN, n = 9). After intratracheal E. coli administration these animals were also ventilated for 6 hrs.
  
  
  RESULTS
  Hypercapnic acidosis protected against evolving pneumonia-induced acute lung injury, attenuating the increase in airway pressure, and the decrement in lung compliance and arterial PO2. However, hypercapnic acidosis did not reduce histologic injury. Hypercapnic acidosis also protected against evolving pneumonia-induced acute lung injury in the presence of neutrophil depletion, reducing both physiologic and histologic indices of lung injury.
  
  
  CONCLUSIONS
  Hypercapnic acidosis reduces indices of intratracheal E. coli induced lung injury by a mechanism that seems to be neutrophil-independent.
authors.affiliation: Department of Anesthesia, Clinical Sciences Institute, National University of Ireland, Galway, Ireland.
authors.forename: Martina
authors.initials: M
authors.lastname: Ni Chonghaile
authors.forename: Brendan D
authors.initials: BD
authors.lastname: Higgins
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Costello
authors.forename: John G
authors.initials: JG
authors.lastname: Laffey
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D055371:Acute Lung Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood / Q000627:therapeutic use; D004195:Disease Models, Animal; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000150:complications* / Q000382:microbiology; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000503:physiopathology*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D018410:Pneumonia, Bacterial / Q000150:complications* / Q000382:microbiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics
chemical_list: D002245:Carbon Dioxide